title: Spacing-out of progestin--efficacy, tolerability and compliance of two regimens for hormonal replacement in the late postmenopause.
abstract: Estrogen replacement therapy with sequential progestin at greater than monthly intervals has been frequently used in practice to reduce progestational side-effects and bleeding episodes, but clinical trials are still lacking. Two new regimens were tested. The main objective was to evaluate efficacy, predominantly in urogenital complaints, tolerability, and patient acceptance. Transdermal estradiol (0.05 mg/day) and norethisterone acetate orally (2.5 mg/day) were administered for 12 days every 2 or 3 months (group A, n = 83, group B, n = 89) to patients whose menopause had begun at least 4 years earlier. Study duration was three long cycles in each group within 7-10 months. Efficacy was good [group A/B = 94/92%], as was systemic tolerability [95/97%]; major skin reactions occurred in 7 and 4%, respectively. Patients' acceptance for continuation of spaced-out treatment was 88 and 87%, respectively. Progestin-associated withdrawal bleedings occurred in 66 (61%) of patients; mean duration 4.3 +/- 1.9/4.8 +/- 1.6 days, with no significant changes during therapy; intensity decreased during therapy. Breakthrough bleeding which required sonographic or histological work-up occurred in 8 and 13%, respectively. Despite the low dosage, transdermal estradiol proved to be efficacious in urogenital complaints. The high acceptance and the reduction of the overall progestin dose to avoid side-effects are of particular prognostic importance with regard to the prevention of cardiovascular diseases. Transdermal estradiol combined with 2- or 3-monthly progestin may be a valid regimen in the late post-menopause, but further studies using spacing-out regimens are urgently needed.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Rabe
authors.forename: A O
authors.initials: AO
authors.lastname: Mueck
authors.forename: F U
authors.initials: FU
authors.lastname: Deuringer
authors.forename: E
authors.initials: E
authors.lastname: Vladescú
authors.forename: B
authors.initials: B
authors.lastname: Runnebaum
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010342:Patient Acceptance of Health Care; D010352:Patient Dropouts; D010865:Pilot Projects; D017698:Postmenopause; D045167:Progesterone Congeners / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000145:classification / Q000517:prevention & control*
chemical_list: D045167:Progesterone Congeners; D004958:Estradiol; D009640:Norethindrone